Department of Pure and Applied Physics, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 169-8555, Japan.
Department of Physics, School of Advanced Science and Engineering, Waseda University, Tokyo, 169-8555, Japan.
Sci Rep. 2021 Jun 4;11(1):11869. doi: 10.1038/s41598-021-91466-y.
We investigated the dominant rule determining synchronization of beating intervals of cardiomyocytes after the clustering of mouse primary and human embryonic-stem-cell (hES)-derived cardiomyocytes. Cardiomyocyte clusters were formed in concave agarose cultivation chambers and their beating intervals were compared with those of dispersed isolated single cells. Distribution analysis revealed that the clusters' synchronized interbeat intervals (IBIs) were longer than the majority of those of isolated single cells, which is against the conventional faster firing regulation or "overdrive suppression." IBI distribution of the isolated individual cardiomyocytes acquired from the beating clusters also confirmed that the clusters' IBI was longer than those of the majority of constituent cardiomyocytes. In the complementary experiment in which cell clusters were connected together and then separated again, two cardiomyocyte clusters having different IBIs were attached and synchronized to the longer IBIs than those of the two clusters' original IBIs, and recovered to shorter IBIs after their separation. This is not only against overdrive suppression but also mathematical synchronization models, such as the Kuramoto model, in which synchronized beating becomes intermediate between the two clusters' IBIs. These results suggest that emergent slower synchronous beating occurred in homogeneous cardiomyocyte clusters as a community effect of spontaneously beating cells.
我们研究了决定小鼠原代和人胚胎干细胞（hESC）衍生的心肌细胞聚类后搏动间隔同步的主要规则。心肌细胞簇在凹琼脂糖培养室内形成，并将其搏动间隔与分散的单个分离细胞进行比较。分布分析表明，簇的同步搏动间隔（IBI）比大多数分离的单个细胞的 IBI 长，这与传统的更快发射调节或“超速抑制”相反。从搏动簇中获得的分离单个心肌细胞的 IBI 分布也证实了簇的 IBI 比大多数组成心肌细胞的 IBI 长。在补充实验中，将细胞簇连接在一起然后再次分离，两个具有不同 IBI 的心肌细胞簇连接并同步到比两个簇的原始 IBI 更长的 IBI，并且在分离后恢复到较短的 IBI。这不仅违反了超速抑制，而且违反了数学同步模型，例如 Kuramoto 模型，其中同步搏动介于两个簇的 IBI 之间。这些结果表明，均质心肌细胞簇中出现了突发的更慢同步搏动，这是自发搏动细胞的群落效应。
